Polycythemia is a normal response to chronic hypoxia at high altitude or from disease; however our understanding of the extent to which or mechanisms by which polycythemia improves oxygen delivery in response to hypoxia is incomplete. It has been assumed that the major benefit is to provide greater oxygen carrying capacity of blood to raise O2 delivery. But recent theoretical considerations suggest that polycythemia also enhances diffusive transport between alveolar air and blood in the lung and between red cells and mitochondria in tissues. Interest also has developed in potential benefits of blood doping in athletes (i.e., blood transfusion to induce polycythemia) as a means to improve athletic performance even in the absence of hypoxia. The latter idea gains credence from the animal kingdom where dogs and horses auto-transfuse themselves by splenic contraction to expand both blood volume and hematocrit during heavy exercise. Our objective is to exploit this natural ability in dogs to determine (1) if spontaneous increases of blood volume and hematocrit (Hct) by splenic contraction enhances maximal O2 uptake, (2) if diffusive transport is an important source of enhancement and (3) if enhancement is greater at simulated high altitude or after pneumonectomy to simulate lung disease. We plan the following comparisons pre and post splenectomy in normal foxhounds and foxhounds after pneumonectomy: 1. Maximal O2 uptake (VO2max); circulating plasma volume and Hct at rest and heavy exercise. 2. Relationships of lung diffusing capacity (DLCO) to cardiac output as workload increases during exercise. 3. O2 diffusing capacity of the lung (DLO2) and distribution of ventilation/perfusion ratios studied with the multiple inert gas elimination technique breathing air and 14% oxygen at increasing work loads. 4. Pulmonary and systemic hemodynamics at rest and exercise. 5. O2 diffusing capacity in tissues (DtO2) estimated from peripheral O2 extraction at peak exercise. After splenectomy comparisons will be made before and after transfusion to restore blood volume to pre-splenectomy levels at peak exercise, (a) at a hematocrit (Hct) of 40% and (b) at a Hct of 55-60% to separate independent effects of Hct and volume. We hypothesize that VO2maz will be reduced after splenectomy, partially restored by (a) and completely restored by (b). We also expect that VO2max will be significantly enhanced by diffusive transport in lung (higher DLCO and DLO2) and tissues (higher DtO2), that enhancement will be greater at simulated altitude than at sea level and that the absence of a spleen will severely impair the compensatory response to pneumonectomy. These studies should help clarify mechanisms and potential extent of compensation by polycythemia to high altitude and cardiopulmonary disease.